The specific binding of [carbonyl-(11)C]WAY-100635 to 5-hydroxytryptamine(1A) receptors was quantitated using different kinetic models. Ten healthy subjects were studied using a GE Advance PET scanner. We suggest that tissue heterogeneity explains part of the nonspecific binding seen in cerebellum, which leads to an underestimation of binding potential with reference tissue methods. The nonlinear three-compartmental model with metabolite-corrected plasma input provides accurate estimates of receptor binding because of the favorable kinetics of tracer in the brain and circulation.