The objective of this investigation was to study the effects of sex steroids on levels of haemoglobin (Hb) and haematocrit (Hct) and to analyse whether these effects can be related to levels of the soluble transferrin receptor (sTfR), a marker of erythropoietic activity. Nineteen male-to-female transsexuals were randomly assigned to either oral ethinyl oestradiol (EE) (n=12) or transdermal 17beta-oestradiol (E2) (n=7); both treatments included the anti-androgen cyproterone acetate (CA). Six male-to-female transsexuals were treated with CA only. Fifteen female-to-male transsexuals were treated with i.m. testosterone esters. The Hct, and levels of Hb, IGF-I, GH and sTfR were measured before and after 4 months of hormone administration. Androgen administration significantly increased the sTfR concentration by 31.5% (P=0.008) and increased levels of Hct, Hb and IGF-I. Both regimens of CA with oral EE and transdermal E2 reduced plasma testosterone similarly to castrate values and decreased Hb and Hct. The CA+oral EE combination induced a decrease in sTfR of 19.0% (P=0.002) which was not the case with CA+transdermal E2 (P=0.27). This cannot be explained by the profound decline in plasma testosterone which was similar with both regimens, but this difference could be related to the different effects of the two regimens on plasma IGF-I. This assumption is supported by the positive correlation that was found to exist between plasma sTfR and IGF-I after the interventions (P<0.05).