Subfertility in lactating cows has a multifactorial background, but a significant cause may be the negative energy balance (NEB) associated with early lactation. One effect of NEB is to delay the interval from calving to first ovulation. The likely candidates for mediating the effects of NEB on reproductive function are the metabolites and metabolic hormones that change in relation to physiological and nutritional state. Circulating IGF-I concentrations fall post partum and both IGF-I and insulin concentrations influence the interval from calving to first ovulation, follicular oestradiol production, and the number of ovulatory oestrogen-active follicles. Moreover, cows with higher IGF-I concentrations after calving generally ovulate within 35 days. Effects of circulating IGF-I on developing follicles are influenced by IGF receptor concentrations and local production of specific binding proteins (IGFBPs). We postulated that severe NEB compromises the early stages of follicular growth via alterations to the follicular IGF system.