The 31-kDa integral membrane protein stomatin (protein 7.2b) is not only an important component of the red cell membrane but can also be found in abundance in different tissues and cell lines. The protein is thought to be anchored to the membrane by a hydrophobic domain while both N and C termini are exposed to the cytoplasm. We have previously shown in the human cell line UAC that stomatin concentrates preferentially in plasma membrane folds and protrusions. There is also evidence that stomatin is linked to the cortical actin cytoskeleton, suggesting a role in cortical morphogenesis of the cell. In this study, we demonstrate that the fundamental structure of stomatin is oligomeric. Whereas interaction of stomatin with itself was suggested by cross-linking experiments, we show by density gradient centrifugation analysis that soluble homo-oligomeric complexes of this protein are present in Triton X-100 extracts of UAC cells. We also show the existence of these oligomers by co-immunoprecipitation of the endogenous stomatin and a recombinantly expressed myc-tagged stomatin, using an anti-myc antibody. The data indicate that these complexes comprise between 9 and 12 monomers of stomatin. Two C-terminally truncated forms of stomatin do not incorporate into these oligomers, suggesting an involvement of the C terminus in the homo-oligomeric interaction.