Abstract Low- (L) and high-yielding (H) variants of A/sw/NJ/11/76 influenza virus were compared for their growth properties in embryonated chicken eggs and MDCK cells and for their binding affinity for the membrane fractions prepared from cells of the chicken embryo allantoic membrane, MDCK, and swine tracheal cells, as well as for soluble sialic acid containing macromolecules and monovalent sialosides. We have shown, that during infection in MDCK cells and in eggs, the progeny of the L variant remain predominantly cell associated, in contrast to those of H. As a result, accumulation of the L mutant in allantoic or culture fluid is significantly slowed in comparison with the H variant. Visualization of the infectious foci formed by the viruses in MDCK cell monolayers and on the allantoic membrane revealed that L spreads predominantly from cell to cell, while the spread of H involves release of the virus progeny into solution and its rapid distribution over the cell monolayer via convectional flow of the liquid. In the binding assays, L displayed significantly higher binding affinity than H for cellular membranes, gangliosides, and sialylglycoproteins, however, the affinity of the variants for the monovalent sialic acid compounds was comparable. Unlike H, L bound strongly to dextran sulfate. The data obtained suggest that all distinctions of the L and H biological phenotypes reported previously [Kilbourne, E. D., Taylor, A. H., Whitaker, C. W., Sahai, R., and Caton, A. (1988) Hemagglutinin polymorphism as the basis for low-and high-yield phenotypes of swine influenza virus. Proc. Natl. Acad. Sci. USA85, 7782–7785] could be rationally explained by a more avid binding of the L variant to the surface of target cells, and that this effect is mainly due to enhanced electrostatic interactions.