The present paper reports complex immunological anomalies associated with motor end-plate disease (Med) in mice. Motor end-plate disease is a severe neuromuscular disorder which leads to death (around the 25th of life) in the Medj/Medj mutant, while the heterozygotes quickly recover from mild manifestations. Medj/Medj and Medj/ + mice share some of the immunological aberrations: reduced PFC response to SRBC in 14-16 day old mice, with reduced suppressor cell function and precocious maturation of the cytotoxic response to allogeneic cells in 21-23 day old mice. The diminished PFC response is corrected in adult Medj/ + mice but persists in the small group of Medj/Medj which escape death and which were studied between the 6th and 16th week of life. In addition, the thymus and spleen of Medj/Medj mice are greatly reduced in size, a symptom which appears with the onset of the clinical disease. Also, a reduction in the NK activity in the small group of older, surviving mice was noted. T and B lymphocyte proportions and the proliferative responses to T cell mitogens were not impaired in 14-16 day old mice. The role of these abnormalities in the pathogenesis of the disease is not known. Since some of these anomalies are shared by Medj/Medj and Medj/ +, the latter of which present no or mild and transient neurological manifestations, there is no clear link between the immunological and neuromuscular disorders.