Nine women taking long-term oral contraceptive steroids (Trinordiol) were studied during a cycle while taking cotrimoxazole (1 gm twice daily) and the results were compared to the previous control cycle. During the cotrimoxazole cycle, there was a significant increase in the plasma concentration of ethynylestradiol (EE). In plasma samples taken on 4 successive days 10-12 hours after dosing, the plasma EE concentration rose from 29.3 +/- 5.0 pg/ml to 38.2 +/- 5.8 pg/ml (mean +/- S.E. P less than or equal to 0.02). In samples taken 24 hours after dosing, the increase was from 18.9 +/- 2.5 pg/ml to 27.8 +/- 4.0 pg/ml (P less than or equal to 0.05). Plasma F.S.H. values in these latter samples, decreased from 4.8 +/- 0.6 mIu/ml to 3.4 +/- 0.5 mIu/ml (P less than or equal to 0.01). No significant changes were noted in the plasma concentrations of levonorgestrel or progesterone. The rise in plasma concentration of EE during cotrimoxazole therapy is attributed to an inhibition of the metabolism of EE by cotrimoxazole as has been shown with other drugs. Short courses of cotrimoxazole are unlikely to cause any adverse effects on contraceptive control when given to women taking long-term oral contraceptive steroids.