Nonpolar regions (hydrophobic nuclei and microclusters) in porcine pancreatic phospholipase A2 have been investigated and described. Based on the atomic coordinates, we analyzed all nonpolar contacts for all nonpolar groups of each amino acid residue and identified three hydrophobic nuclei (gamma 1, gamma 2, gamma 3) and four microclusters (mu 4, mu 5, mu 6, mu 7) in the enzyme. These nonpolar regions include hydrophobic residues as well as residues with charged or polar side chain. Quantitative characteristics of hydrophobic nuclei show that the latter are condensations of nonpolar contacts in the protein. The stability of the nuclei is comparable to that of the secondary structure elements. Comparative analysis of nonpolar areas in native porcine pancreatic phospholipase A2, mutant enzyme, and its complex with a substrate analog demonstrated the role of nonpolar contacts in protein structure and function.