Heat-induced inactivation of bovine plasmin, denaturation of beta-lactoglobulin (beta-lg), the interactions between both species and casein micelles and the subsequent net effect on proteolysis of beta-casein was studied in a model system consisting of phosphocasein and beta-lg in synthetic milk ultrafiltrate. The inactivation of plasmin and denaturation of beta-lg were first order reactions, with the rate of inactivation of plasmin being greater than the rate of denaturation of beta-lg. The predominant mechanism involved in the denaturation of plasmin in the temperature range 65-80 degrees C was its interaction with beta-lg (V at 60 degrees C, 0(.)0526; E-a, 176 KJ/mol). At the point of complete inactivation of plasmin similar to 45% of the beta-lg remained undenatured. Thermal inactivation of plasmin through other mechanisms was negligible. The association of beta-lg with the casein micelles at 60 degrees C had a rate constant of 3(.)71 X 10(-5) min(-1) and an E-a of 259 KJ/mol; thermal denaturation of beta-lg was of much less importance, with a rate constant at 60 degrees C of the order of 1 x 10(-10) min(-1) and an E-a of 250 KJ/mol. On denaturation of all beta-lg in the system, a maximum of similar to 55% was associated with the casein micelles. The effect of heating on the subsequent hydrolysis of beta-casein indicated that the level of plasmin activity was the most important factor affecting proteolysis, while the interaction of beta-lg with the casein micelles had limited effect. Overall, thermal stability of plasmin in milk is very much dependent upon its interaction with beta-lg.