The localization of mouse C1q in various mouse tissues was assessed by immunohistochemistry. In all mouse strains examined, C1q was associated with cells in small focal areas of lymph nodes, Peyer's patches, and spleens often near germinal centers. Ultrastructural studies of these foci demonstrated that C1q was present in the endoplasmic reticulum of mononucleated cells that had an extensive cytoplasmic network. Occasionally, small deposits of C1q were observed in the perinuclear space of mononucleated cells that had scanty cytoplasm with few organelles. Extracellular C1q was found at the surface of interdigitating cell processes in these lymphatic foci. In addition to the presence of C1q within lympho-reticular tissues, C1q frequently was detected in renal glomeruli but not in urinary tract epithelium or intestinal epithelium of adult mice; in contrast, C1q was localized in the intestinal epithelium of neonatal mice. C1q was not detected in tissue fibroblasts nor in cultured fibroblasts; however, a subpopulation of mouse adherent peritoneal cells maintained in vitro did contain C1q. The results of these studies provide new information regarding the distribution and, thus, the possible sites of C1q biosynthesis in normal mouse tissues.