In a comparative study absorption and elimination characteristics of p.o. administered paromomycin and neomycin were investigated in healthy volunteers and patients with liver cirrhosis and/or portocaval shunt. Serum and urine concentrations were determined by means of the diffusion test. 1. In a cross-over study 6 volunteers were each administered single p.o. doses of 14.28 g paromomycin sulfate (= 10 g free base = 1.6 X 10(-2) mol) and 16 g neomycin sulfate (= 10.65 g free base = 1.7 X 10(-2) mol). Following these virtually equimolar doses AUC values of neomycin were 2.5 times as high as those of paromomycin (p less than 0.01). Paromomycin serum level time courses could be described by an open one-compartment model with a mean half-life of 2.6 h (harmon. mean). Mean computed maximum levels of 3.6 microgram/ml appeared on an average of 1.9 h after administration. After 32 h the mean recovery in urine was 0.2%. 5 volunteers showed a similar behavior with a mean excretion of 0.1%, whereas one person excreted 0.8% in urine. The time course of neomycin was evaluated according to an open two-compartment model with a distribution half-life of 1.5 h and a terminal half-life of 9 h (harmon. means). Mean computed maximum levels of 5.1 microgram/ml appeared on an average of 2.6 h after administration. The mean lag time was 1.3 h. 32 h after administration 0.3% of the dose were detected in urine. 2. Patients with cirrhosis and/or portocaval shunt were treated with 8 capsules/d of either 357.1 mg paromomycin sulfate or 250 mg neomycinsulfate each over a period of 7 days. Despite the lower dose of neomycin comparable serum levels of both aminoglycosides were observed. This result can be explained by a lower elimination rate and a higher extent of accumulation of neomycin. Mean amounts excreted in the urine of the 7th day were 0.1% for paromycin and 0.2% for neomycin.