The insertion/(I)/deletion (D) polymorphism of the angiotensin-converting enzyme gene (ACE) is of increasing interest in etiology and treatment of various neuropsychiatric disorders. The present study aimed to replicate own earlier findings that depressive patients with the ACE D-allele are responding better to treatment with antidepressants than those with the II genotype. We further investigated a common polymorphism (A1166C) in the angiotensin II receptor gene (AT1) to examine a possibly combined influence. A sample of 273 patients with major depression, being treated with different classes of antidepressants, was enrolled in the study. Genotyping was carried out using a polymerase chain reaction and snapshot method, respectively, and the severity of depression was monitored using the HAMD-17 scale before and after 4 weeks of treatment. The ACE II genotypes showed poorer improvement in HAMD-17 scale after 4 weeks of treatment (ANOVA: F=4.49, p=0.01) than carriers with one or two D-alleles. Similarly, more than 70% of the AT1 CC homozygotes had a 50% reduction in the HAMD-17 scale within 4 weeks of treatment. Our data might further suggest that patients with a haplotype combining the CC and DD/ID genotypes respond better to treatment than those with either single allele. These results should however be replicated in future research.