We have grown 7 bona fide non-HeLa contaminated cell lines in the cheek pouch of immunosuppressed adult hamsters. Six of the cell lines studied produced or continued to express the chorionic form of alkaline phosphatase under these conditions. The Regan isoenzyme produced in culture by the J82, T24, HCT-8, and COLO 16 cell lines disappeared in vivo with a concomitant appearance of the chorionic isoenzyme. The other cell lines, however, maintained the expression of the Regan isoenzyme when grown as a xenograft: the C41 line produced the Regan isoenzyme in culture, and continued to do so in vivo, while the BeWo cells, which synthesized the chorionic enzyme in culture were induced by in vivo growth to produce both the Regan and chorionic isoenzymes. No expression of the oncoamniotic (FL) isoenzyme was observed in any of the lines studied. Our results indicate a convergence of human tumor xenografts with respect to the production of the chorionic form of alkaline phosphatase. Furthermore, the loss of production of the Regan isoenzyme was seen in most, but not all cell lines studied. Since the oncoamniotic (FL) isoenzyme was only observed by HeLa cells growing as a xenograft, the expression of this enzyme form may be a HeLa specific phenomenon. We must now look to the regulation of the chorionic isoenzyme as the most promising avenue of approach to understanding the biological significance of altered isoenzyme expression in human tumor xenografts.