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In ecological field surveys, observations are gathered at different spatial locations. The purpose may be to relate biological response variables (e.g., species abundances) to explanatory environmental variables (e.g., soil characteristics). In the absence of prior knowledge, ecologists have been taught to rely on systematic or random sampling designs. If there is prior knowledge about the spatial patterning of the explanatory variables, obtained from either previous surveys or a pilot study, can we use this information to optimize the sampling design in order to maximize our ability to detect the relationships between the response and explanatory variables? The specific questions addressed in this paper are: a) What is the effect (type I error) of spatial autocorrelation on the statistical tests commonly used by ecologists to analyse field survey data? b) Can we eliminate, or at least minimize, the effect of spatial autocorrelation by the design of the survey? Are there designs that provide greater power for surveys, at least under certain circumstances? c) Can we eliminate or control for the effect of spatial autocorrelation during the analysis? To answer the last question, we compared regular regression analysis to a modified t‐test developed by Dutilleul for correlation coefficients in the presence of spatial autocorrelation. Replicated surfaces (typically, 1000 of them) were simulated using different spatial parameters, and these surfaces were subjected to different sampling designs and methods of statistical analysis. The simulated surfaces may represent, for example, vegetation response to underlying environmental variation. This allowed us 1) to measure the frequency of type I error (the failure to reject the null hypothesis when in fact there is no effect of the environment on the response variable) and 2) to estimate the power of the different combinations of sampling designs and methods of statistical analysis (power is measured by the rate of rejection of the null hypothesis when an effect of the environment on the response variable has been created). Our results indicate that: 1) Spatial autocorrelation in both the response and environmental variables affects the classical tests of significance of correlation or regression coefficients. Spatial autocorrelation in only one of the two variables does not affect the test of significance. 2) A broad‐scale spatial structure present in data has the same effect on the tests as spatial autocorrelation. When such a structure is present in one of the variables and autocorrelation is found in the other, or in both, the tests of significance have inflated rates of type I error. 3) Dutilleul's modified t‐test for the correlation coefficient, corrected for spatial autocorrelation, effectively corrects for spatial autocorrelation in the data. It also effectively corrects for the presence of deterministic structures, with or without spatial autocorrelation. The presence of a broad‐scale deterministic structure may, in some cases, reduce the power of the modified t‐test.