Most cells in the normal adult mouse thymus express Thy-1 glycoprotein but do not express Pgp-1 glycoprotein. In contrast, cells of the mouse B-cell lineage are Thy-1 negative and Pgp-1 positive. Somatic cell hybrids between pseudodiploid Thy-1+, Pgp-1- T-cell lymphomas and pseudotetraploid Thy-1-, Pgp-1+ Abelson-leukemia-virus-induced cell lines do not express detectable cell-surface Thy-1 but show activation of the T-cell Pgp-1 glycoprotein. Hybrids between pseudodiploid lines, in contrast, show extinction of Pgp-1. Thy-1+ or Pgp-1+ revertants were isolated by cell sorting from hybrids in which extinction occurred, demonstrating that all genes required for expression of these cell-surface antigens were present in antigen-negative hybrids. Thy-1- hybrids did not contain detectable cytoplasmic Thy-1 messenger RNA, while Thy-1 message could be detected in parental lines and Thy-1+ revertants. No obvious rearrangements of the Thy-1 structural genes could be demonstrated in Thy-1- hybrids and their Thy-1+ revertants, nor could rearrangements be demonstrated when parental cells and Thy-1- hybrids were compared. These results are consistent with the idea that diffusible gene products regulate both Thy-1 and Pgp-1 expression in these hybrids. These products act in a gene dosage-dependent manner in somatic cell hybrids. Regulation of Thy-1 is at the level of either messenger RNA transcription or processing.