1. 1. Uroporphyrinogen I synthase (UPGI-S) was purified from bovine erythrocytes to 1300 fold and from human to 400 fold. 2. 2. Six UPGI-S isoenzymes were separated from both bovine and human erythrocytes. 3. 3. Stability experiment indicated there were two groups among human UPGI-S isoenzymes: (1) low stability-high activity (SH1-SH3) and (2) high stability-low activity (SH4-SH6). 4. 4. UPGI-S isoenzymes SH1, SH2 and SH3 were the major portion of total UPGI-S activity for human, while for bovine isoenzymes, SB4, SB1 and SB6 were the major component in the enzyme activity.