Spontaneous bacterial peritonitis (SBP) is a well defined clinical syndrome with a high mortality (50 to 95%). It is among the most serious complications of cirrhosis. The prevalence of SBP is usually set at about 8% in cirrhotics with aseites, although there are recent reports of up to 18% of such patients. A retrospective study was conducted at R.E. Thomason General Hospital, E1 Paso, Texas, in which all paracentesis performed on the Medicine Service from January 1983 to June 1986 were reviewed. A diagnosis of SBP was made if the ascitic fluid fulfilled one or more of the following criteria: neutrophilic leukocytes, > 250/ul; Gram stain and /o r culture, positive for microorganisms. A diagnosis of SBP was made in 32 patients, all male, with a mean age of 40 years (range, 28 to 66). The manifestations at the time of diagnosis were: jaundice, 100%; increased abdominal girth, 88%; general weakness, 68%; abdominal pain, 46%; and fever, 40%. All of the patients had severe alcoholic liver disease with 69% falling into Child's class C. Pending results of ascitic fluid culture, 18 patients (56%) received either cefazolin or cephapirin, nine (28%) received ampicillin plus an aminocyclitol, and five (16%) received cefotaxime. Ascitic fluid cultures yielded bacteria in 12 cases: five Escherichia coli (41%); two Streptococcus pneumoniae; and one Enterobacter spp., Klebsiella spp., Proteus spp., Serratia spp., and Campylobacter spp. Susceptibility testing (Microscan) indicated 58% of the isolates were susceptible to cefazolin and 91% to cefotaxime. The combination of ampicillin with an aminocyclitol was active against 100% of the bacterial isolates. Forty-four percent (4 out of 9) of the patients who received an aminocyclitol developed deterioration of renal function. It is not clear whether this complication was in fact nephrotoxicity from the aminocyclitol drug or evidence of hepatorenal syndrome. Twenty-two patients (69%) died, yielding a mortality rate of 91% (11 out of 12) for culture-positive cases, and 55% (11 out of 20) for patients with culturenegative ascitic fluid. In patients who responded to treatment, a second paracentesis was carried out 48 hours after antimicrobics were started. All showed at least a 50% reduction of neutrophilic leukocytes in the ascitic fluid. The signs and symptoms of SBP are largely independent of the offending organism, and it is not surprising that SBP remains under diagnosed. Even with enhanced clinical awareness, diagnosis is difficult because most patients do not have either fever or abdominal pain. In the past, once a diagnosis of spontaneous bacterial peritonitis was made, we usually began treatment with cefazolin or cephapirin. Change in treatment could not be based on laboratory data for about 72 hours-the time required for carrying out identification and susceptibility testing. According to our recent experience, the earlier cephalosporins cannot be relied upon for the empiric treatment of SBP. In our group of patients with severe alcoholic liver disease and SBP, ampieillin plus an aminocyclitol provided complete coverage, but the risk of nephrotoxicity was unacceptably high. The newer cephalosporins, eg, cefotaxime, provided activity comparable to that of ampicillin plus an aminocyclitol, without the problem of toxicity. Recently published reports validate our experience. A second paracentesis 48 hours after starting treatment was helpful in assessing the patient's response to therapy.