Pancreatic D-cell disorder was analyzed in Coxsackievirus B4-induced diabetic mice employing molecular hybridization with a radiolabelled probe to quantitate somatostatin mRNA, and specific immunoprecipitation to measure somatostatin synthesis and its release. Many infected mice showed blood glucose lower than noninfected control animals at 72 h postinfection and 85% became hyperglycemic at 6-8 weeks postinfection. Pancreatic somatostatin decreased by 24% and 43% at 72 h and 6 weeks postinfection, respectively, while somatostatin release in islets from the infected mice increased by 2-fold or more. Residual islet somatostatin content after release was initially higher than control at 72 h and then declined at 6 weeks. Islet cellular RNA content decreased by 35% at 6 weeks, somatostatin mRNA content decreased by approximately 45% at 72 h and 6 weeks postinfection. D-cell disorder - somatostatin mRNA supply, synthesis, and release - is clearly evident in this model, which could be of significance in type I diabetes.