The purposes of this study were to test the negative association between schizophrenia and rheumatoid arthritis(RA) and to clarify the role of prolactin and estrogen as protective factors in this association. The author compared the prevalence rate of RA between 561 patients with schizophrenia and 222 patients with mood disorder. For investigating the role of estrogen and prolactin, the author checked the plasma prolactin and estradiol level in 80 patients with paranoid schizophrenia and 77 patients with RA. The results were as follows. 1) Epidemiological data The prevalence rate of RA in the schizophrenic group was 0/561 and that of RA in the mood disorder group was 2/222. To compare these results between two groups, the author applied the Binomial test using the average prevalence rate of RA(0.8%) in the general population as a reference rate. The prevalence rate of RA in the schizophrenic group was significantly lower than that of RA in the general population. However, the prevalence rate of RA in the mood disorder group was not significantly different to that of RA in the general population. 2) Comparison of plasma prolactin and estradiol level between two groups The plasma level of prolactin in the schizophrenic group was significantly higher than that of prolactin in the RA group(p=0.000). However, the plasma level of estradiol in the schizophrenic group was significantly lower than that of estradiol in the RA group(p=0.017). These results were not consistent across gender. To contrast with the results in the female group, which were consistent with the results in the total subjects, for the male group, the plasma levels of prolactin and estradiol in the schizophrenic group were significantly higher than those of prolactin and estradiol in the RA group. These results support the results of previous studies which confirm the negative association between schizophrenia and RA. These results also suggest that the elevation of plasma prolactin level in the patients with schizophrenia has a antirheumatic effect while the elevation of plasma estradiol level in the patients with RA has a anti-schizophrenic effect, and that these effects act as a possible mechanism in the negative association between two disorders. However, these results suggest that this association is specific to female patients.