Estradiol treatment of sexually immature Sprague-Dawley, Cr:NIH-nu/+ and Cr:NIH-nu/nu rats for 2 days results in a significant increase in the number of uterine eosinophils and OX-42 positive macrophages. However, only Sprague-Dawley rats exhibit an estrogen regulated increase in the number of cells expressing immunoreactive CD4 and Ia, suggesting that the differential responsiveness to the effects of estradiol between the two strains of rats may be genetically controlled. Nevertheless, Cr:NIH-nu/nu rats, which are deficient in T-cells, possess virtually identical numbers of CD4 positive staining uterine cells as compared to their nu/+ littermate controls, indicating that the expression of immunoreactive CD4 is associated with a resident non-T-cell population. In addition, a message for rat CD4 was observed in Northern blots of uterine mRNA, suggesting that the immunoreactive CD4 expressed by uterine cells is probably a fully functional cell surface antigen/receptor rather than a truncated form which only expresses the antigenic determinant recognized by the W3/25 monoclonal antibody.