Since trimethoprim-sulfamethoxazole (TMP-SMX) was first marked occasional reviews have surveyed the pattern of adverse reactions. Skin rashes characteristic of sulfonamide sensitivity have predominated, with relatively few of a serious exfoliative nature. Hematologic adverse reactions recorded follow the pattern known to occur with sulfonamides, with a few cases related to the action of trimethoprim on human folate metabolism. Such an effect is more likely to occur when the patient's folate status is already jeopardized; it is rare in relation to the widespread use of the drug combination. Long-term administration does not per se seem to represent an additional hazard provided the dose is the correct one and the hematologic monitoring of the patient is performed regularly. The suggestion that TMP-SMX has a toxic effect on the kidney has not been substantiated. An estimated 250 million "standard treatment courses" have been given in the first 6 years of marketing and, overall, the picture of adverse reactions corresponds with that expected from a sulfonamide of relatively low toxicity.