Northern blot analysis of poly(A)(+)RNAs isolated from mouse liver or mouse testis (Te)/epididymis (Ep) reveals that both tissues express 1.5- and 7.5-kb transcripts which have extensive homology to the major form of the rat asialoglycoprotein receptor (ASGP-R). In situ hybridization studies have localized the expression of this ASGP-R-like transcript to late-stage sperm from Te and Ep of several different strains of mice. Swiss Webster mice express this ASGP-R-like transcript in late-stage spermatids at the time of release into the seminiferous tubule and in Ep sperm, while Balb/C, NIH Swiss and C57Bl/6 mice express this ASGP-R-like transcript predominantly in Ep sperm. cDNAs containing the entire coding region for this ASGP-R-like transcript have been cloned from mouse liver and mouse Te/Ep. These cDNAs are 100% identical in the coding region and 3'-untranslated region (UTR), but differ in the 5'-UTR. The gene encoding these cDNAs is called MHL-1, designating the major form of the mouse ASGP-R. The deduced amino acid (aa) sequence of MHL-1 shares 88% homology to the rat hepatic (He) lectin form 1 (RHL-1) and 78% homology to the human asialoglycoprotein receptor form 1 (H1). The three sites for N-linked glycosylation in the RHL-1 sequence are all conserved in the deduced MHL-1 sequence. Taken collectively, these data describe the cloning and sequencing of the MHL-1 cDNA and illustrate its deduced aa homology to RHL-1 and H1. Most importantly, these data show that mouse late-stage spermatids and Ep sperm express the authentic MHL-1 gene, suggesting this receptor may have an important role in spermatogenesis, in addition to its He function.