We have studied the expression of transforming growth factor beta-1 (TGF-beta 1) RNA during mouse tooth development, using in situ hybridization and experimental tissue recombinations. Analysis of the serial sections revealed the appearance of local expression of TGF-beta 1 RNA in the dental epithelium at bud-staged teeth (13-day embryos). Just before transition to the cap stage, TGF-beta 1 RNA expression rapidly increased in the epithelial bud, and it also extended to the condensed dental mesenchyme. At cap stage (14- and 15-day embryos), there was an intense expression of TGF-beta 1 RNA in the morphologically active cervical loops of the dental epithelium. During early bell stage (16- and 17-day embryos), TGF-beta 1 RNA expression was detected in the inner enamel epithelium where it subsequently almost disappeared (18-day embryos). After birth TGF-beta 1 transcripts transiently appeared in these cells when they were differentiating into ameloblasts (1-day mice). The transcripts were lost from the ameloblasts when they became secretory (4-day mice), but the expression continued in ameloblasts in enamel-free areas. Transient expression of TGF-beta 1 RNA was also detected in epithelial stratum intermedium cells at the time of ameloblast differentiation. In the mesenchyme, TGF-beta 1 RNA was not detected during bell stage until it appeared in differentiated odontoblasts (18-day embryos). The secretory odontoblasts continued to express TGF-beta 1 RNA at all stages studied including the odontoblasts of incisor roots. Analysis of the distribution of bromodeoxyuridine (BrdU) incorporation indicated apparent correlations between TGF-beta 1 RNA expression and cell proliferation at the bud and cap stages but not at later stages of tooth development. Tissue recombination experiments of bud-staged (13-day embryos) dental and non-dental tissues showed that tooth epithelium, when cultured together with tooth mesenchyme, expressed TGF-beta 1 RNA. When the tooth epithelium was combined with non-dental jaw mesenchyme, TGF-beta 1 transcripts were not expressed. However, TGF-beta 1 RNA expression was seen in oral epithelium cultured with dental mesenchyme, while no expression of TGF-beta 1 transcripts was seen in the oral epithelium during normal development. Thus, TGF-beta 1 RNA expression seems to be regulated by epithelial-mesenchymal interactions.