1. The urinary excretion of sulphamethoxazole and its metabolites was compared between healthy volunteers and HIV-seropositive patients in order to get a better understanding of why HIV seropositives are more predisposed to idiosyncratic toxicity of sulphonamides. 2. A single 800 mg oral dose of sulphamethoxazole was administered to seven healthy volunteers and seven asymptomatic HIV seropositives without previous use of sulphonamides. 3. Urine was collected for 4 days and drug analysis was by h.p.l.c. 4. No difference was observed between seropositive and seronegative individuals in the urinary recovery of sulphamethoxazole, N4-acetyl-, 5-hydroxy-, N4-acetyl-5-hydroxy-sulphamethoxazole and the N1-glucuronide conjugate. However the recovery of the hydroxylamine metabolite of sulphamethoxazole was significantly lower in the HIV seropositives (0.50 +/- 0.51 vs 2.23 +/- 0.85%; 95% CI on the difference, -0.90 to -2.55; P = 0.0006). 5. Sulphamethoxazole hydroxylamine may be a factor in the susceptibility of HIV infected individuals to sulphonamides.