Histamine (HA) increases prolactin (PRL) release in adult male and female rats. This response depends on the age of the animals and some differences were appreciated between male and female rats. At 20 days of age the PRL response was greater than earlier ages. This response was studied and the type of HA receptor that may be involved in the mediation of this PRL response was defined. Animals of both sexes, at 5 or 20 days of age, were injected into the lateral brain ventricles with 3 log-doses of histamine (HA), 2,2,pyridilethylamine (2 PEA, and H1-histamine agonist), 4 methyl-histamine (4 MHA, an H2-histamine agonist) or saline as control. Fifteen minutes later a sample of blood was taken from the jugular vein and plasma PRL levels were determined by RIA [radioimmunoassay]. HA induces an increased PRL release in 20-day-old animals. This response was not identical in rats of both sexes. Female rats appeared to be more sensitive to HA than male rats. 2 PEA, was not able to reproduce the response in male rats but it was effective in female animals. 4 MHA induced the response in both sexes in a similar way than HA. At 5 days of age in male rats HA had no effect on PRL release. In female rats, instead, only the greater dose was able to induce a small but statistically significant response. Neither 2 PEA nor 4 MHA were able to stimulate the PRL release at this age. H2-histamine receptors are present in male rats and in female animals both types of receptors may be involved in the control of PRL release.