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Methods and results are reviewed of research on the permeability of the vagina to a wide variety of compounds including steroids, prostaglandins (PGs), antimicrobials, proteins, antigens, and hormones, nonoxynol-9, methadone, and inorganic compounds. Although the literature indicates that the vagina is capable of absorbing a wide variety of organic and inorganic compounds, quantitative data on the extent of absorption are often lacking. Most steroids were readily absorbed and their bioavailability after intravaginal instillation was greater than after oral administration because of a reduced first-pass effect. Natural and synthetic PGs were absorbed; the extent of absorption ranged from 10-43% of the dose. Penicillin and sulfanilamide exhibited extremely variable absorption from the vagina. In most women neither econazole, miconazole, nor clotrimazole were effectively absorbed. In 1943 it was demonstrated that proteins could be absorbed from the vagina. Data on human absorption of nonoxynol-9 are indirect but are consistent with absorption. Methadone, povidone-iodine, and potassium permanganate have also been shown to be absorbed through the vagina. The stage of the reproductive cycle may alter the extent of vaginal absorption, but this has been clearly demonstrated for only 1 substance in the rat.