Serotonin S2-receptors were solubilized from human brain by means of the mild detergent, lysolecithin. Previous studies have shown that the serotonin S2-receptors in human brain are mainly enriched in the cortex. A total particulate fraction from human cortex was treated with 0.25% lysolecithin. [3H]Ketanserin binding sites from the soluble extract showed the binding characteristics of S2-receptors: potent 5HT antagonists like pirenperone, methysergide and pipamperone competed for [3H]ketanserin binding at nanomolar concentrations. The agonists bufotenin and serotonin themselves were more active than the potent dopamine agonist tetraline. Binding was saturable with a low KD (1.07 nM) and reversible. There was a good correlation between the drug potencies in both soluble and membrane preparations and also with the IC50 values previously obtained in membrane preparations and soluble extract from rat brain. Therefore, lysolecithin allows serotonin S2-receptors from human brain to be obtained in a molecularly dispersed form with the same high affinity properties as in the original membranes.