We have investigated the effects of multiple 2-hourly injections of LH-releasing hormone (LHRH) on the number and size of the gonadotrophs and gonadotroph secretory granules, and the lipid content of gonadotrophs in the pituitary glands of intact and gonadectomized male and female hypogonadal (hpg) mice. Gonadotrophs were identified by immunocytochemistry for LH beta, and the size and secretory status of the gonadotrophs were assessed by quantitative ultrastructural analysis of immunoidentified gonadotrophs. The administration of 60 ng LHRH by subcutaneous injection every 2 h for 15 days resulted in an increase in the number, size and granule content of LH beta-immunoidentified gonadotrophs of hpg mice to values found in normal adult mice. Large lipid droplets accumulated in 30-40% of the gonadotrophs in both male and female LHRH-treated hpg mice. Although lipid-containing gonadotrophs were larger than lipid-free cells in all LHRH-treated groups irrespective of the presence or absence of gonads, a marked difference in the number, position within the cell, and size of the secretory granules between the lipid-containing and lipid-free cells was found only in the pituitary glands of intact LHRH-treated hpg females. These results demonstrate: (a) that the effects of multiple injections of LHRH on the morphology of the gonadotrophs of hpg mice is not dependent on the presence of functioning gonads, although ovarian factors are required for the full development of morphological, and hence possibly functional, heterogeneity in the gonadotroph population in female animals, and (b) that, although multiple injections of LHRH in hpg mice are more effective than single daily injections of LHRH in stimulating pituitary-gonadal function, there is no obvious difference in the morphologically recognizable effects that these two modes of administration have on the pituitary gonadotrophs.