Retinoic acid (RA) is a metabolite of vitamin A that exists as several biologically active isomers including all-trans RA and 9-cis RA. The receptors for all-trans RA and 9-cis RA are members of the steroid hormone family of receptors. Two classes of RA receptors, the retinoic acid receptors (RARs) and the retinoid X receptors (RXRs), have been identified. Both receptors classes have three subtypes: α, β and γ. All-trans RA binds primarily to the RARs, while 9-cis RA is the primary ligand for the RXRs. We have previously shown that both all-trans RA and 9-cis RA regulate surfactant protein SP-A, SP-B and SP-C gene expression in human fetal lung explants cultured in vitro for five days and SP-B gene expression in the H-441 cell line, a human pulmonary adenocarcinoma epithelial cell line. We hypothesized that the RARs and RXRs are present in human fetal lung tissue and in the H-441 cell line. We used the reverse transcriptase-polymerase chain reaction and oligonucleotide primers specific for the α, β and γ isoforms of RARs and RXRs to detect mRNA for these receptors in undifferentiated, mid-trimester human fetal lung tissue, in fetal lung explants maintained for five days in vitro and in the H-441 cell line. In undifferentiated human fetal lung tissue, both RARβ and RARγ were both present; RARα was not detected. However, in cultured fetal lung explants, all RAR isoforms were detected although RARα was present in only trace amounts. RXRα, RXRβ and RXRγ were detected in both the undifferentiated fetal lung tissue and in fetal lung explants cultured for five days. The fetal lung tissue consists of both connective tissue and epithelium, therefore we also determined the retinoid receptor status of a pulmonary epithelial cell line which produses two of the surfactant proteins, SP-A and SP-B. Both RARβ and RARγ were present in the H-441 cell line; RARα was not detected. RXRα, RXRβ and RXRγ were all detected in the H-441 cell line. We conclude that RARs and RXRs are present in human fetal lung tissue and in the H-441 pulmonary epithelial cell line and speculate that the retinoids all-trans RA and 9-cis RA regulate surfactant protein gene expression via these receptors.