Purpose. Transforming growth factor beta (TGF-β) isoforms 1 and 2 have recently been detected in stimulated human tear fluid. The purpose of this study was to determine if these TGF-βs are produced and secreted by the lacrimal gland.Methods. To accomplish this, reverse transcriptase polymerase chain reaction (RT-PCR) was used to detect expression of TGF-pl and TGF-β2 mRNAs in normal human and rabbit lacrimal gland biopsies. Northern blot analyses were used for comparing the relative levels of expression of these TGF-βmRNAs in rabbit lacrimal glands. Human lacrimal gland biopsies were evaluated by immunohistochemistry for production of TGF-β1, TGF-β1 latency associated peptide (LAP), and TGF-β2 proteins. Super-natants of unstimulated and carbachol-stimulated human lacrimal gland explant cultures were evaluated for secretion of TGF-β1 and TGF-β2 by ELISA.Results. TGF-β1 and TGF-β2 mRNA expression was found in all human and rabbit lacrimal gland specimens by RT-PCR. A greater level of expression of TGF-β1 than TGF-β2 mRNA in the rabbit lacrimal gland was noted by Northern blot. In human lacrimal gland biopsies, TGF-β1 and TGF-β1 LAP were detected in acinar and ductal epithelia by immunohistochemistry. TGF-β2 specific antibodies stained a small percentage of acinar and ductal epithelia, as well as material within the lumens of tubulo-acinar complexes in one-third of these glands. TGF-β1 was detected in supernatants of human lacrimal gland explants, and the concentration of TGF-β1 increased by an average of 280% after carbachol-stimulation (p = 0.004). TGF-β2 could not be detected in unstimulated or stimulated human lacrimal gland explant supernatants.Conclusions. The results of these experiments indicate that TGF-βl and TGF-β2 are produced by and TGF-β1 is secreted by the human lacrimal gland. They also suggest that the lacrimal gland may be one source of TGF-βin human tear fluid.