Two matching groups of schizophrenic patients refractory to conventional therapies were given methionine and hydroxychloroquine, respectively, following two base periods. Significant differences were observed in improvements and release rates and in the Standardized Affect Conveying Test. The methionine group showed exacerbation of symptomatology, while the hydroxychloroquine group showed amelioration of symptoms. The eosinophils and lymphocytes showed downward trend in the methionine group and so did the skin reactivity to intradermal injections. These results support the hypothesis that the schizophrenic process is exacerbated by increased effort readiness without discharge, as enhanced by methionine administration. The significant ameliorating effect of hydroxychloroquine is offered as a tool for therapeutic studies.Abstract Teaser