Burgeoning evidence suggests that the hormone relaxin modulates collagen in the extracellular matrix of diverse tissues. In separate lines of study, we provide further substantiation of this hypothesis. Immunofluorescence was used to probe isolated fibroblasts derived from volar oblique ligament explant culture for vimentin, actin, RXFP1, and estrogen receptor beta. Ligaments were obtained as surgical waste from thumb reconstruction patients. Four specimens have been examined to date. Cells derived from these patients expressed vimentin and actin, consistent with fibroblast morphology. Putative fibroblasts derived from two of three female patients expressed RXFP1 receptors; the solitary male was negative. Given the small sample, however, the data are considered preliminary. Immunohistochemistry was used on frozen sections from 26 skin biopsies obtained from children undergoing genitoplasty. A subset of samples was also probed for transforming growth factor (TGF-beta1) and TGF-beta3. Appropriate controls were used. Finally, a subset of patient blood was assayed for relaxin by using an enzyme-linked immunosorbent assay-based method. The results showed RXFP1 receptor expression in the cells that populate the basement membrane in 96% of patients, regardless of gender. Most tissue expressed TGF-beta. Finally, serology suggested that relaxin was detectable in these children. Our two lines of research provide additional evidence for the diverse tissue tropism of relaxin. In particular, connective tissues as diverse as ligaments and basal lamina keratinocytes express RXFP1. These data lend support to our contention that relaxin affects ligament integrity and wound healing.