In view of the lack of unanimity on the effect of longterm intake of combined oral contraceptives (OC) on external sodium-dependent lithium efflux, otherwise known as sodium-lithium countertransport (SLC), we undertook a double-blind study to investigate the possible interaction between SLC and OC in healthy women with regular menstrual cycles.In a group of 17 volunteers, aged 27.0 ± 1.1 years (mean ± s.e.m.) and weighing 61.4 ± 2.0 kg, ingestion of 30 g ethinyloestradiol + 150 g desogestrel for 3 months caused an increase in SLC activity from a baseline value of 0.254 ± 0.017 mmol/lcell.h to 0.274 ± 0.017 mmol/lcell.h (P = 0.05). The activity of the transport system after 6 months treatment remained higher than at baseline (0.280 ± 0.016 mmol/lcell.h, P Ͻ 0.025) but was comparable to that at 3 months.