Calcium is essential for the maintenance of contraction in the heart, and it has been suggested that the glycoprotein matrix on the external surface of cardiac cells is a critical factor in the supply of 'activator' calcium to the beating heart. Sialic acid residues are important calcium-binding sites in the matrix and treatment with neuraminidase, an enzyme which cleaves sialic acid from oligosaccharide chains, has been reported to abolish spontaneous contraction in cultured heart cells, without causing general breakdown in the plasma membrane. However, we report here that in intact, electrically stimulated guinea pig atrial preparations, neuraminidase treatment produces no significant changes in resting tension or force of contraction. It is also without effect on the response to calcium removal and replacement, and inotropic or toxic concentrations of cardiac glycosides. In these experiments, up to 79% of the total tissue sialic acid was removed, and electron microscopy studies showed that this removal was accompanied by marked reduction of lanthanum binding to the sarcolemma. We therefore conclude that the calcium-binding sialic acid residues in the external matrix of the cardiac cells are of little importance in the maintenance of contractile function in these intact atrial preparations.