Basement membrane zone gene expression by fibroblast cultures established from adult human skin was examined by molecular hybridizations with human sequence-specific cDNAs corresponding to pro-alpha 1 (IV) chain of type IV collagen and B2 chain of laminin. Northern transfer analysis of poly(A)+RNA isolated from fibroblast cultures clearly revealed the presence of specific mRNA transcripts, indicating the expression of the genes coding for pro-alpha 1 (IV) and laminin B2 polypeptides. Quantitative estimates of the relative levels of these mRNAs coding for basement membrane zone components indicated that they are of relatively low abundance in control fibroblasts, as compared with mRNAs coding for fibronectin or pro-alpha 1 (I) chain of type I procollagen. In fibroblast cultures established from the lesional skin of a 32-year-old patient with lipoid proteinosis, the levels of mRNA coding for pro-alpha 1 (IV) polypeptides were increased approximately 4.5-fold, as compared with age- and passage-matched control cultures. This increase was selective in that the levels of fibronectin, pro-alpha 1 (I), and beta-actin mRNAs were unaltered in the same cultures. The increase in pro-alpha 1 (IV) mRNA level was also uncoordinate with the expression of the laminin B2 chain gene, which was unaltered in lipoid proteinosis. The selective increase in pro-alpha 1 (IV) mRNA may have relevance to the accumulation of this basement membrane component in the skin in lipoid proteinosis.