Intrafetal insulin-like growth factor-I (IGF-I) promotes cardiac hypertrophy in the late gestation fetal sheep; whether these effects are sustained is unknown. IGF-I was infused for 4 days at 80 µg/h from 121-125 days gestation and its effects at 128 days, 3 days after the infusion stopped were determined by comparison with untreated fetal sheep. After IGF-I treatment, fetal weights were similar to controls but kidney weights were bigger (P<0.05) as were spleen weights of male fetuses (P<0.05). Fetal cardiac myocytes were larger in female than male fetal sheep (P<0.001). IGF-I increased male myocyte volumes (P<0.001) but not female. IGF-I did not alter the proportions of uni or binucleated right or left ventricular myocytes. Female fetal sheep had a greater proportion of binucleated cardiac myocytes than males (P<0.05). IGF-I treated fetuses had a slightly greater proportion of right ventricular nuclei in cell cycle phase G2/M, and a reduced proportion of G0/G1 phase nuclei (P<0.1). Therefore evidence for IGF I stimulated cardiac cell hyperplasia in fetal sheep in late gestation was limited. In conclusion, the greater sizes and larger proportion of binucleated cardiac myocytes in female fetal sheep suggests that myocyte maturation may occur earlier in females than in males. This may explain in part the male sex specific responsiveness of cardiac hypertrophy to IGF-I in late gestation. If IGF-I stimulated cardiomyocyte growth is accompanied by maturation of contractile function, IGF-I may be a potential therapeutic agent for maintaining cardiac output in preterm males.