The form of 125I-labeled membrane alloantigens (I-Ak and H-2Kk) and immunoglobulin M shed by murine splenic lymphocytes labeled by lactoperoxidase-catalyzed radioiodination was determined by gel chromatography and ultracentrifugation. I-Ak and H-2Kk antigens are shed as particles ranging in size from 3 X 10(5) to 2 X 10(6), whereas membrane IgM is shed as an individual unit consonant with its native size of 180,000. The effects of detergents on the size of shed I-Ak and H-2Kk and the coprecipitation of (3H) lipids with these proteins suggest that I-Ak and H-2Kk are shed in association with local membrane lipids as small membrane-derived vesicles, whereas membrane IgM is shed without detectable associated lipid.