Sera from 100 patients not infected with Serratia marcescens at the time of hospital admission lacked detectable H-immobilizing antibodies against all 20 currently recognized H-antigens of this microorganism. However, various patient sera revealed elevated titers of O-agglutinins against several of the 20 O-antigens of S. marcescens, in a particular O-antigens, O1, O3, O4, O5, O7, O8, O10, O11, O16, O17, O18, O19, and O20. Rabbit anti-Shigella serogroup B immune serum cross-reacted with S. marcescens O-antigens O1 and O10; anti-Shigella serogroup C serum cross-reacted weakly with S. marcescens O-antigen O8. Conversely, rabbit anti-S. marcescens O1 and O10 immune sera cross-reacted with a clinical isolate of Shigella flexneri. None of the anti-S. marcescens O1-O20 rabbit immune sera reacted with commercial febrile antigens of Salmonella serogroups A, B, C1,2, D, E1,2,3,4, Brucella abortus, Francisella tularensis, and Proteus OX19. However, a reference strain of Salmonella typhi (9;d,-) was agglutinated by anti S. marcescens anti-O8 and O10 sera, a reference strain of S. paratyphi B (4,5;-,-) weakly by anti-S. marcescens O8 serum, and a reference strain of S. paratyphi C (6,8;-,-) by anti-S. marcescens anti-O10 and O16 rabbit immune sera. None of the anti-S. marcescens H-antisera cross-reacted with H-antigens of S. typhi (o;d,-), S. paratyphi A (1,2;a,-), S. paratyphi B (4,5;b,0), S. choleraesuis (6,7;-,1,5), typhimurium (4,5;,i,-), and S. enteritidis (9;gm,-). Yersinia enterocolitica reference strain Ye 75 (OI = O3) eas agglutinated weakly by anti-S. marcescens O2 serum, whereas Y. enterocolitica reference strain Ye 373 (OV = O9) cross-reacted with S. marcescens anti-O5 rabbit immune serum. Intravenously and tissue cage-infected rabbits developed anti-H and anti-O-antibodies within 5 to 12 days after infection with representative test strains of S. marcescens. Therefore, it is suggested that the serodiagnosis of human S. marcescens infections consist of serial monitoring of both anti-H and anti-O agglutinins, because determinations of the latter alone might yield false-positive, i.e., potentially misleading results.