Co-trimoxazole (trimethoprim-sulfamethoxazole) is a commonly prescribed antimicrobial agent. Although it is well tolerated in most patients, serious adverse events related to its use have been described. Hypoglycaemia is a rare but potentially life-threatening complication of therapy. We describe a case of refractory hypoglycaemia complicated by seizure associated with co-trimoxazole for the treatment of Pneumocystis carinii pneumonia in a patient with AIDS. We also review 13 previously reported cases of co-trimoxazole-induced hypoglycaemia. Among this patient population, renal insufficiency was the most prevalent predisposing risk factor (93%). The mean daily dose of co-trimoxazole was 4.5 double strength (160 mg trimethoprim/800 mg sulfamethoxazole) tablets per day. Serum insulin levels were raised or inappropriately normal in 88% of cases in which they were measured, suggesting a sulfonylurea-like effect of co-trimoxazole as the mechanism of hypoglycaemia. All cases required intravenous glucose administration, and 43% experienced protracted (>12 hours) hypoglycaemia. Dosage adjustments should be made when prescribing co-trimoxazole to patients with renal dysfunction.