Serum free thyroxine (FT4) and total thyroxine (TT4) levels were measured at 2-week intervals during the course of hospitalization in 29 male inpatients in the following four diagnostic groups: paranoid schizophrenia (PS); undifferentiated schizophrenia; bipolar I disorder, manic; and major depressive disorder, endogenous type. The most striking finding was a difference in the direction of both TT4 and FT4 change during clinical recovery in the PS group compared with the other three groups. Analysis of the delta values, representing the change between admission and discharge values, revealed significant differences between the mean rise in the PS group vs. the mean decreases in the other three groups for both TT4 (p less than .0003) and FT4 (p less than .003). For TT4, 75% of the PS group showed a rise during recovery in contrast to 4% of the remaining groups; for FT4, 50% of the PS group showed a rise compared with 14% of the other groups. A significant difference was also observed between the FT4 levels of bipolar I, manic vs. PS patients at the time of hospital admission, which may have potential usefulness in the differential diagnosis of these two disorders. This study emphasizes the importance of exploring more fully the psychiatric significance of thyroxine levels within the endocrinological normal range and of doing longitudinal assessments of thyroxine and symptom changes during clinical recovery in psychiatric disorders.