Many xenobiotics containing N or S heteroatoms are metabolized by the cytochrome P450s, leading to a variety of products which can be toxic, carcinogenic, or detoxifying. Thus, it is important to try to establish molecular criteria that modulate competitive product formation for these types of compounds. In the absence of 3D structures for the P450 isozymes that are responsible for the oxidations of N- and S-containing compounds, we have focused here on the characterization and identification of possible electronic and thermodynamic factors that could be modulators of different types of product formation. Specifically, the competition among N-oxidation, N-hydroxylation and Cα-hydroxylation for three amines were examined. Similarly, three thioethers were studied for their internal competition between S-oxidation and Cα-hydroxylation. The results obtained indicate that the stability of the cation radical intermediate formed by the one electron transfer mechanism is not a determinant of differences in product distribution between the two types of compounds. Rather, relative product stability appears to be a significant modulator of product distribution explaining why S-oxide formation is favored over N-oxide and why Cα-hydroxylation is usually favored over N-oxide formation in amines. © 1993 John Wiley & Sons, Inc.