Direct and indirect ELISA differ in their primary antibody use. In a direct ELISA, the primary antibody is labeled and directly binds to the antigen. In an indirect ELISA, an unlabeled primary antibody binds to the antigen, and a labeled secondary antibody is used to detect the primary antibody. Indirect ELISA is more versatile as it can detect multiple antibodies in one test, while direct ELISA is used when the primary antibody is limited or difficult to label. The choice between them depends on the specific experimental goals.