A search for expression of heat-stable placental-type alkaline phosphatase (ALP) has been carried out in 19 unselected human tumor cell lines, known not to be HeLa. All cell lines showed measureable ALP activity and in 15 of the lines at least low levels of a heart-stable, presumptively placental-type ALP were detected. In five of these lines where the level of this heat-stable activity was sufficient, further, investigation, (immunologic, inhibition and electrophoretic studies) demonstrated that this ALP was placental-type in its characteristics and clearly different from liver/bone/kidney or intestinal ALPs. In 10 lines the heat-stable activity was too low to allow further characterization, In four lines no heat-stable activity in these various lines was liver-bone-kidney in type. This study suggests that the placental ALP locus may be expressed in at least at low levels in a much higher proportion of tumors and tumor cell lines than previously reported. The findings taken together with recent reports that low levels of placental-type ALP are present in some normal adult tissues (cervix, Goldstein et al., 1980; testis, Chang et al., 1980), indicate that so-called "ectopic" synthesis of placental ALP in tumor cells may not necessarily be due to derepression of a structural locus which is completely unexpressed in normal adult tissues. It may represent an enhancement of expression in malignancy or there may be clonal expansion of a particular cell type which normally expresses the alkaline phosphatase at a high level.