The excretory-secretory (E-S) products and surface antigens of 19 isolates of Giardia were compared by reactivity of E-S products with antisera to homologous and heterologous organisms and by acrylamide gel electrophoresis of surface-labeled Giardia. Isolates could be divided into three broad groups on the basis of the previously reported DNA studies and the present studies. Group 1 consisted of five isolates with similar or highly cross-reactive E-S. These showed identical DNA banding patterns after endonuclease restriction analysis; four of five had identical surface antigens, and the remaining isolate showed a similar but different major surface antigen. Group 2 consisted of 11 isolates with moderate reactivity amongst themselves. DNA patterns showed some bands in common with group 1 organisms and themselves, but the surface-antigen molecular weight patterns were different. Group 3 consisted of three isolates with reactivity only amongst themselves. There were no DNA bands in common with group 1, and the molecular weights of the surface antigens were diverse. Surface-antigen differences are common among isolates of Giardia lamblia. These differences correlated to some degree with the DNA banding patterns observed after endonuclease restriction analysis and may result in altered virulence and host response.