A general model for estimating the number of amino acid substitutions per site (d) from the fraction of identical residues between two sequences (q) is proposed. The well-known Poisson-correction formula q = e (-d) corresponds to a site-independent and amino-acid-independent substitution rate. Equation q = (1 - e(-2d)/2d, derived for the case of substitution rates that are site-independent, but vary among amino acids, approximates closely the empirical method, suggested by Dayhoff et al. (1978). Equation q = 1/(1 + d) describes the case of substitution rates that are amino acid-independent but vary among sites. Lastly, equation q = [ln(1 + 2d)]/2d accounts for the general case where substitution rates can differ for both amino acids and sites.