The effect of vegetation size upon the concentration of antibiotic within various points of a fibrin-clot heart valve vegetation such as ones found in bacterial endocarditis was examined. A mathematical model based upon Fick’s second law of diffusion was developed and solved on a PDP-11 computer. The antibiotic was assumed to have a half-life of 30 min and intermittently injected intravenously every 4 h. After 5 simulated antibiotic doses, peak and trough levels of the antibiotic near the center of the vegetations of sizes 0.5, 1.0, 2.0 cm were, respectively, 37 and 3%, 22 and 15%, and 18 and 18% of the free serum antibiotic concentration. This model can be used to estimate antibiotic levels in different areas of a valvular vegetatio