Many antimicrobial agents have been associated with hypoprothrombinemia. The precise mechanisms are unknown, but alteration in vitamin K status or utilization is involved. The two postulated mechanisms implicate either direct inhibition of biosynthesis of the vitamin K-dependent clotting factors by the N-methylthiotetrazole (NMTT) moiety found in certain antimicrobial agents or eradication of vitamin K-producing intestinal microflora in patients with reduced oral intake of vitamin K. An English-language review of all prospective studies reported between 1966 and 1988 in which serial prothrombin times were monitored in adult patients revealed that the incidence of hypoprothrombinemia varied from 3.7% to 64% with NMTT-containing regimens and from 0% to 24% with non-NMTT-containing regimens. Detailed evaluation of these and other studies suggests that certain risk factors, including malnutrition, hepatic and renal dysfunction, older age, and severity of illness, may be the major determinants of hypoprothrombinemia. The hypothesis that the NMTT side chain is primarily responsible for hypoprothrombinemia may not be justified. We conclude that patients at high risk for coagulopathy should be carefully monitored and that serious consideration should be given to the use of prophylactic vitamin K in such cases.