Human-derived lactobacilli were isolated from fecal samples of healthy volunteers. Forty-six isolates from different volunteers were selected and investigated for their immunomodulatory properties. Conditioned medium from each isolate was assessed for its effect on tumor necrosis factor (TNF) production in lipopolysaccharide-activated THP-1 monocytes. Of 46 Lactobacillus isolates, 12 significantly inhibited TNF production in varying magnitude. Lactobacillus strain TH58 displayed the most potent TNF-inhibitory activity (70% inhibition). In contrast, Lactobacillus strain TH14 exhibited immunostimulatory property by activating TNF production in THP-1 monocytes. Lactobacillus TH14 induced nuclear factor-kappaB (NF-kappaB) activation in the absence of lipopolysaccharide stimulation, whereas Lactobacillus TH58 had no effect on NF-kappaB signaling, irrespective of lipopolysaccharide stimulation. Strain TH58 was identified as Lactobacillus saerimneri and strain TH14 as Lactobacillus ruminis by sequence analysis of their 16S rRNA genes. This is the first report of a human isolate of L. saerimneri with TNF-inhibitory activity and L. ruminis, an indigenous species to humans, with TNF stimulatory activity. Our data suggest the potential use of these two strains as immunoprobiotic candidates.