Aims: To investigate the possible association and gene–gene interaction effects of polymorphisms in NMDA receptor subunit (GRIN1, GRIN2A and GRIN2B) and dopamine receptor (DRD1, DRD2 and DRD3) genes with clozapine response. Materials & methods: GRIN1 rs11146020 (G1001C), GRIN2A GT-repeat and GRIN2B rs10193895 (G-200T) polymorphisms were tested for association in a Caucasian (n = 183) and an African–American (n = 49) sample using χ² and ANOVA tests. Logistic regression and two-way ANOVA were used to explore gene–gene interaction effects with dopamine receptor gene variants. Results & conclusion: This study does not support the involvement of the NMDA receptor subunit gene polymorphisms in clozapine response. All tests for an association were negative. Gene–gene interaction analyses however yielded promising leads, including an observed effect between DRD1 rs686 and DRD3 Ser9Gly polymorphisms on clozapine response (p = 0.002). Original submitted 29th September 2010; Revision submitted 4th November 2010.