We assessed the relation between serotonin 5-HT2 receptor availability and aging and compared it with that for dopamine D2 receptors on 19 healthy male volunteers (age range, 21-49 years) using positron emission tomography (PET) and F-18 N-methylspiperone (NMS). 5-HT2 Receptor availability was obtained using the ratio of the distribution volume in the region of interest to that in the cerebellum (Bmax'/Kd' + 1). 5-HT2 Receptor measures were obtained in frontal and occipital cortices. D2 receptor availability in striatum was measured using the "ratio index". 5-HT2 Receptor availability decreased significantly with age. This effect was significantly more accentuated for 5-HT2 receptor availability in the frontal (r = 0.92, p < or = 0.0001) than in the occipital (r = 0.67, p < or = 0.0016) cortex (df = 1, p < 0.025). Dopamine D2 receptors were also found to decrease significantly with age (r = 0.63, p < or = 0.007). In a given subject, striatal D2 receptor availability significantly correlated with 5-HT2 receptor availability in the frontal (r = 0.51, p < or = 0.035) but not in the occipital cortex. These results document a decline in 5-HT2 and D2 receptor availability with age and showed an association between frontal 5-HT2 and striatal D2 receptors.