The present study was undertaken to quantify the immunocytochemical changes for thyrotropin-releasing hormone (TRH) within the ventral horn of the cervical spinal cord from Wobbler (wr/wr) mice selected at postnatal ages 3 weeks to 5 months compared with the normal phenotype (NFR/wr) littermates as well as mice from two related normal mouse strains: the NFR/N parent strain, and the closely related C57Bl/6N mouse strain. The immunoreactive (IR) neuronal processes containing TRH appeared in all specimens within Rexed's laminae VIII, IX, and X. Compared with the normal (C57Bl/6N, NFR/N) specimens, the pair-matched normal phenotype (NFR/wr) and Wobbler (wr/wr) specimens possessed significantly greater numbers of IR-TRH containing processes at every age studied. Compared with the normal phenotype (NFR/wr) specimens, greater numbers of IR-TRH containing processes appeared in the ventral horn region studied from the Wobbler (wr/wr) specimens taken early (Stage 1) as well as later (Stages 3 and 4) in the motoneuron disease. An age-related decline in the number of IR-TRH processes was apparent among the specimens from the Wobbler mouse strain (NFR/wr, wr/wr), but not the normal (NFR/N, C57Bl/6N) mouse strains. The data suggest that TRH may play a significant role in the Wobbler disease, possibly even before the symptoms become apparent. In addition strain-related differences exist which may be important to the etiology of the Wobbler disorder.