The meaning of heterogeneity in schizophrenia and the impact of genetic and environmental factors on etiology are a matter of continuous debate in psychiatric research. Different clinical and birth history variables were investigated in a sample of 68 patients with chronic catatonic schizophrenia according to DSM III-R, classified into Leonhard's systematic schizophrenia (n = 32) and periodic catatonia (n = 36). Parental transmission of the disease was evident in 44% of the periodic catatonia cases compared to one case in systematic catatonia (3%; p = 0.0003). In systematic catatonia, 34% of the index cases were exposed to prenatal infections compared to 8% in periodic catatonia (p = 0.008). Using logistic regression analysis exposure to gestational maternal infections predicted diagnosis of systematic catatonia at p = 0.008, and parental psychosis predicted diagnosis of periodic catatonia in the index cases at p = 0.0001. The latter finding is substantiated by the recent mapping of a periodic catatonia-susceptibility locus on chromosome 15q15 with evidence for autosomal dominant transmission. These findings support the hypothesis that distinct schizophrenia phenotypes are based on different etiological mechanisms.