Serum free thyroxine (FT4), total thyroxine (TT4), and Brief Psychiatric Rating Scale (BPRS) measurements were obtained following hospital admission and at 2-week intervals during hospitalization in 80 male psychiatric inpatients with a variety of major psychotic and affective disorders. A strong correlation between the range values for BPRS sum and for FT4 (p less than 0.005) and TT4 (p less than 0.001) levels indicated that change in overall symptom severity was linked to change in thyroxine levels during clinical recovery. We found the relationship not to be a simple one, but to require definition of criteria for three patient subgroups for each hormone, taking into account the initial absolute thyroxine level, as well as the direction and magnitude of hormonal change during recovery. The hormonally defined "good recovery" subgroup included patients with high initial thyroxine levels that then fell substantially, patients with low initial thyroxine levels that then rose substantially, and patients with initial thyroxine levels in the middle range that subsequently changed substantially. The hormonally defined "poor recovery" subgroup included those patients not meeting these criteria. The degree of clinical improvement in the hormonally defined good recovery group was significantly greater by almost twofold than the poor recovery group both for FT4 (p less than 0.04) and TT4 (p less than 0.02). These findings suggest that a "normalizing" principle underlies the relationship between clinical recovery and thyroxine levels and that both FT4 and TT4 levels within the normal range appear to have clinical significance in either reflecting or contributing to the course of a variety of psychiatric disorders and possibly having a role in pathogenesis.