The effect of thyroid status on histamine H1 receptors in adult and developing rat brain was investigated using the (3H) mepyramine binding assay. Hypothyroidism induced by treatment with 6-n-propyl-2-thiouracil resulted in a 31% decrease in the density and total content of adult rat brain (3H) mepyramine binding sites and a significant retardation of the developmental increase in H1 receptor binding in neonates. At 30 days of age, when euthyroid rats reached binding levels of the adult, hypothyroid animals presented reductions of 22 and 39% in (3H) mepyramine bound per unit weight and per brain respectively. In contrast, hyperthyroidism induced by treatment with L-thyroxine did not alter H1 receptor numbers in the adult rat brain but accelerated the developmental increase in (3H) mepyramine bound per unit weight that reached normal adult levels by 21 days of age. The results suggest that thyroid dysfunction during early life and adulthood may cause derangements of the histaminergic system in the brain.