Close monitoring of adverse reactions to the trimethoprim-sulfamethoxazole combination reported over four years since marketing, during which more than 25 million standard 20-tablet courses have been administered, shows the pattern and relative incidence of adverse reactions expected from a sulfonamide of low toxicity. There have, so far, been no adverse reactions attributable to direct toxic effects, and the cutaneous sensitivity and hematologic reactions seem to be based on an immunologic rather than directly toxic etiology. The evidence so far available does not indicate that the drug in routine use in the recommended dosage could induce a state of deficiency in regard to folate metabolism. No unusual or unexpected reactions have been encountered so far. Clinical experience with the combination of trimethoprim and sulfamethoxazole does not give cause for any undue concern about its safety in the recommended use.