Previous studies have identified no consistent change in sex hormone binding globulin (SHBG) levels during normal menstrual cycles. This is despite marked cyclical changes in plasma oestradiol concentration, and the observation that SHBG level increases in pregnancy, and after administration of exogenous gonadotrophin or synthetic oestrogens. The level of SHBG was measured in 19 normal females at 2 d intervals from day -8 to +10 where the preovulatory peak of oestradiol was designated as occurring on day 0. SHBG levels increased by a mean 15% +/- 4 (SEM) between the follicular and luteal phases (P less than 0.001) and this was due entirely to an increment between day 0 and +2. The change in SHBG levels was correlated with the change in oestradiol levels between days -8 and 0 (P less than 0.001). Fifty-six infertile patients were also studied. Twenty-seven received Pergonal alone whilst the other 29 received Pergonal after a preceding 5 d on Clomid. In both groups peak preovulatory oestradiol levels were greater than 3 times higher than in normal cycles. SHBG levels showed no change in the follicular phase but rose markedly during the luteal phase. These increases were significantly correlated with peak preovulatory oestradiol concentration but showed no relationship with mid-luteal progesterone concentration. We conclude that supranormal levels of oestradiol cause marked increases in SHBG binding capacity and increases in SHBG level of a lower order occur shortly after the preovulatory peak of oestradiol in the normal menstrual cycle.