Texas Star-SR, a laboratory-derived mutant of Vibrio cholerae El Tor Ogawa 3083, which produces B but not A subunit of cholera toxin was given to 68 healthy adult volunteers in doses of 10(5) to 5 X 10(10) organisms. 16 of 68 exhibited loose stools but in only one individual was stool volume notable. Vomiting occurred in 1 and abdominal cramps in 3 vaccines; malaise and fever were not seen. Texas star was recovered from stools of 22% who received low doses (10(5) or 10(6) organisms) and from 63% who received high doses (10(8), 10(10), 2 X 10(10) or 5 X 10(10)). The attenuated strain was also recovered from jejunal fluid of 76% in the high dose group; cultures revealed 10(2)-10(5) organisms/ml. Seroconversions of vibriocidal antibody occurred in 93% and peak organisms/ml. Seroconversions of vibriocidal antibody occurred in 93% and peak titers were resembling those seen following clinical cholera. In contrast, serum IgG ELISA antitoxin rose significantly in only 29% and levels were below those encountered after clinical cholera. Only 5 of 18 vaccinees tested so far had significant rises in intestinal SIgA antitoxin; these also manifested rises in serum antitoxin. The occurrence of loose stools did not correlate with dose ingested, excretion of vibrios or rise in serum antitoxin. 503 clones recovered from coprocultures and jejunal fluids were negative when tested for enterotoxin. One month following a single 5 X 10(10) organism dose of Texas Star, 7 vaccinees and 6 controls were challenged with 10(6) pathogenic El Tor Ogawa vibrios. Diarrhea occurred in 7 of 10 controls but in only 1 of 7 vaccinees (p = 0.05). Despite clinical protection, excretion of pathogenic V. cholerae was similar in vaccinated and control groups. Twelve vaccinees who received two 10(9) or two 2 X 10(10) organisms doses of Texas Star 1 week apart were challenged with 10(6) pathogenic V. cholerae El Tor of the heterologous serotype. Diarrhea occurred in 11 of 15 controls but in only 3 of 12 vaccinees (p. 0.01). The 3 vaccinees with diarrhea all had mild illness. Texas Star-SR is a prototype that commonly causes mild diarrheal responses but is genetically stable in vivo and stimulates protective immunity against challenge with either the homologous or heterologous serotype.