Abstract In an effort to analyse the contribution of individual serotonin and dopamine receptor subtypes to antipsychotic medication response, we analysed the correlation between clinically effective antipsychotic drug dose and binding affinity to cloned serotonin and dopamine receptor subtypes. Clinically effective dosage and binding affinity to the D2 dopamine receptor subtype were moderately correlated for typical antipsychotic medications (r=0.57, p=0.04), and were similarly modestly correlated for atypical antipsychotic drugs (r=0.66, p=0.07). Surprisingly for typical antipsychotic medications, a stronger inverse correlation was observed between drug dosage and 5-HT2C affinity (r=−0.65, p=0.03). The strongest correlation observed for typical antipsychotic medications was between medication dose and 5-HT2C/D2 binding affinity ratio (r=−0.81, p=0.002). For atypical antipsychotic medications, highly significant correlations were observed between medication dose and receptor-binding affinity to D3 dopamine receptor (r=0.78, p=0.02), and with the ratios of D2/5-HT1A (r=0.85, p=0.009), D3/5-HT1A (r=0.78, p=0.021), D2 (5-HT2A/5-HT1A) (r=0.75, p=0.033) and D3 (5-HT2A/5-HT1A) (r=0.75, p=0.03) receptor-binding affinities. The correlation between medication dose and D2 (5-HT2C/5-HT1A) receptor-binding affinity ratio was of similar magnitude (r=0.70, p=0.055). No significant correlations were identified between atypical antipsychotic medication dose and 5-HT1A, 5-HT2A, 5-HT2C, 5-HT2C/D2 or 5-HT2A/D2 receptor-binding affinities. These observations suggest an interaction between D2 and 5-HT2C receptor-binding effects contributing to the therapeutic response achieved following treatment with typical antipsychotic medications. This suggests that for typical antipsychotic medications, constitutive serotonin 5-HT2C receptor signalling interacts with and facilitates the antipsychotic benefit achieved through dopamine D2 receptor blockade. Additionally, this analysis demonstrates that, in contrast to typical antipsychotic medications, the therapeutic effectiveness of atypical antipsychotic medications results from opposing interactions among three distinct domains: (1) antipsychotic potency is enhanced by increased D2 and D3 dopamine receptor-binding affinity; (2) antipsychotic efficacy is also facilitated by increased binding affinity to serotonin 5-HT2C and 5-HT2A receptors; (3) in contrast, antipsychotic potency is reduced by elevations in 5-HT1A receptor-binding affinity.