Eight healthy, male subjects participated in a balanced randomized crossover study to investigate the effect of a course of co-trimoxazole (CT; combination of sulphamethoxazole 800 mg and trimethoprim 160 mg, twice daily for 5 days) on the pharmacokinetics and urinary metabolite profile of an orally administered dose of theophylline (TH). There were no significant differences (p greater than 0.05) between the control and treatment phases with respect to any of the following pharmacokinetic parameters of TH: area under the plasma total TH concentration time curve; fraction unbound in plasma; area under the plasma unbound TH concentration time curve; terminal half-life; apparent volume of distribution; apparent total plasma clearance and renal clearance. The urinary recoveries of 1-methyluric acid, 1.3-dimethyluric acid and of theophylline were not significantly different (p greater than 0.05) between the two study phases. There was a significant difference (p less than 0.05), however, in the urinary recovery of 3-methylxanthine (11.3 +/- 2.6 per cent TH alone versus 13.9 +/- 3.6 per cent TH-CT) and in the total urinary recovery of TH and its metabolites (76.5 +/- 8.2 per cent versus 85.3 +/- 7.0 per cent), the latter finding suggesting that CT may have caused a small increase in the extent of TH absorption. The results of the study indicated that CT did not inhibit the biotransformation of TH.