The development of multi-drug resistance by enteric bacteria is an increasing problem in the developing countries. There is need to monitor antimicrobial susceptibility of these organisms in order to ensure appropriate treatment and control of infections. Antimicrobial susceptibility patterns, plasmid DNA content and restriction enzyme digests of plasmid deoxyribonucleic acid (DNA) were used to study 175 Salmonella and Shigella species isolated from predominantly HIV-seropositive adult patients in Nairobi, Kenya. All the isolates were sensitive to ciprofloxacin. A significantly higher proportion of Shigella species were resistant to chloramphenicol, cotrimoxazole, streptomycin and tetracycline compared to Salmonella species (p-value < 0.001). Multi-resistant Salmonella typhimurium isolates had 60, 40 and 5 MDa plasmids, the 5 MDa plasmid was absent in gentamicin sensitive isolates. In addition to 2-10 MDa range of plasmids, multi-resistant Shigella species had a heavy 100-105 MDa plasmid. Restriction enzyme digests were similar for the 60 and 40 MDa plasmid DNA bands from Salmonella typhimurium isolates but did not show any consistency among Shigella spp. Plasmid-encoded multi-drug resistance plays a major role in the spread of resistance among enteric bacteria. It is vital to use drugs rationally in order to control the emergence and spread of multi-drug resistance.