Administration of anti-TNFα antiserum enhanced a sublethal infection with salmonellae of moderate virulence (Salmonella typhimurium M525) in innately susceptible (Itys) BALB/c mice, indicating that TNFα is important in the early response which suppresses bacterial growth in the reticuloendothelial system (RES). However, only transient low levels of TNFα were detectable on day 3 in sera from some, but not all, sublethally infected mice. Conversely, on day 4 of the same infection, clear TNFα inhibitory activity was detected in some sera. Neither TNFα or any inhibitory activity were detected in sera of lethally infected BALB/c mice undergoing an acute, overwhelming Salmonella infection. In contrast, TNFα inhibitory activity, but not TNFα, was detected in sera of mice showing a cachectic syndrome induced by persistent high bacterial numbers following intravenous inoculation of a very high dose (2 × 107) of the attenuated aro-S. typhimurium SL3261 strain. © 1992.