SummaryAdverse reactions to various trimethoprim‐sulphonamide (T‐S) combinations were studied retrospectively in dogs and cats referred to the Utrecht University Department of Clinical Sciences of Companion Animals during the period 1985–1994. Dermatological and systemic reactions were observed in 19 dogs and 2 cats. Specific histological reaction patterns were seen in 3 dogs with toxic epidermal necrolysis, in 1 dog and 1 cat with erythema multiforme, and in 1 dog with pemphigus foliaceus. Diagnostic criteria used in humans proved to be reliable in dogs and cats as well. Adverse reactions were observed within 7–14 days after administration and were most often due to sulphadiazine (76%) and sulphatroxazole (14%). The incidence of adverse reactions to T‐S was 0.25%.