Different heat inactivation rates were found among the three common homozygous human placental alkaline phosphatase phenotypes with respect to component I (the rapidly migrating component). Phenotype I1 was less stable than F1 and S1, while types F1 and S1 exhibited very similar thermostabilities, F1 being slightly more stable than S1. Components I, IIα (the fastest of the slow-moving components), and IIβ (the group of the very slowly migrating components) had different heat stabilities, IIβ being the most stable and I the least stable. Magnesium greatly increased the heat stability of all tested phenotypes. Placental alkaline phosphatase was found to be less heat resistant than reported previously. All phenotypes were equally inhibited over urea concentrations ranging from 0.5 to 8 m. No difference in the inhibition rate was found among components I, IIα, IIβ, and the crude placental butanol extract. The altered electrophoretic pattern of the crude placental extract obtained by urea starch gel electrophoresis was considered as being most likely due to reversible changes in the folding of the molecules.