The whey acidic protein (WAP) promoter has been previously used to target the expression of heterologous genes to the mammary glands of transgenic mice. To direct the expression of human GH (hGH) to mouse mammary glands, hGH-coding sequences have been coupled to WAP promoter sequences (WAP-hGH). Female transgenic mice carrying the WAP-hGH constructs show expression of hGH in the mammary gland, demonstrating the functionality of the transgenes. However, when other organs from these transgenic mice were examined, high level expression of hGH was unexpectedly observed in the brains of all male and female mice. Using in situ hybridization or immunohistochemistry, hGH expression from the transgene was seen to occur specifically in Bergman glia cells. In contrast, mice carrying hGH-coding sequences linked to the metallothionein promoter do not express hGH in these cells. Neither the endogenous WAP gene nor at least three other transgenes in which heterologous genes have been placed under the transcriptional control of the WAP promoter are expressed in the brain. Thus, we propose that the combination of the WAP promoter and the hGH structural gene results in a novel tissue specificity in the Bergman glia.