Age-related changes in histamine H1 receptors were studied using [11C]pyrilamine or [11C]doxepin by positron emission tomography (PET). The frontal, parietal and temporal cortices showed age-related decreases in binding of approximately 13% per decade. In contrast, the thalamus showed no apparent decrease in binding during normal ageing because of its higher nonspecific binding. Post mortem studies also indicated that the nonspecific binding of [3H]pyrilamine in the thalamus was approximately 112% higher than that in the cortex. However, no significant decrease in histamine H1 receptors with age was observed by in vitro binding assays of autopsied human frontal cortex. Possible reasons are given for the larger effects of age observed in the PET study than in the in vitro post mortem binding study.