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Low-dose weekly methotrexate (MTX) is widely used in the treatment of rheumatoid arthritis1 and is now increasingly used in other rheumatic conditions, including systemic lupus erythematosus and juvenile arthritis. Because of its anti-metabolic and cytotoxic actions, questions of its safety in those of childbearing age are likely to become increasingly important. The aim of this review is to aid clinicians in the counselling and education of patients taking or about to start taking low-dose MTX. We examine the effects of MTX with respect to fertility, pregnancy and lactation, based upon information obtained using `Medline' search strategies from 1966 to 1997, hand search through the last ten years of the journal Teratology, source paper references and data from the UK National Teratology Information Service (NTIS) from 1992. MTX is a derivative of the folic acid analogues. The importance of folic acid, a B group vitamin, in haematopoiesis was realized in the early 1940s, and by 1946 it had been synthesized and given its chemical term, pteroylglutamic acid.2 By the following year, the synthesis, anti-bacterial and anti-metabolic actions of its 4-amino derivative, aminopterin, had been described.3 The megaloblastic appearance of marrow in some cases of leukaemia, similar to that seen in folic acid deficiency, led early researchers to speculate that folic acid analogues could be useful in treating this form of malignancy. Paradoxically, it was found that a folate-deficient diet could cause depletion of leukaemic cell lines, which led to the use of the competitive analogues in haematological malignancies.4 In 1951, aminopterin was used for the first time for patients with a connective tissue disease, with six out of seven patients with rheumatoid arthritis experiencing some benefit. The authors commented, `The toxic effects of aminopterin place practical limitations on its use as a therapeutic agent'.5 MTX (amethopterin) … Dr M.E. Lloyd, Department of Rheumatology, Frimley Park Hospital, Portsmouth Road, Frimley, Surrey GU16 5UJ