Increasing sociopolitical concerns with antibiotic use have led to investigations of potential alternatives for food safety and growth promotion. Direct-fed microbials (DFM) including spore-based probiotics are amenable to feed inclusion and are extremely stable. We isolated several Bacillus spp. from environmental and poultry sources and tested them for their ability to reduce Salmonella in vitro. In a preliminary in vivo trial, day-of-hatch chicks and poults were randomly assigned to the following treatments (24 birds/treatment): control and one of 8 DFM candidates at 10(6) spores/g of feed. Chicks and poults were tagged, weighed, and orally challenged with Salmonella Typhimurium (ST). Body weight gain and ST recovery were measured 11 d posthatch. Total percentages of ST-positive crop and ceca were significantly lower (P < 0.05) in at least 3 DFM candidates compared with control. Additionally, beneficial effects on BW gain were observed in at least 5 DFM candidates (P < 0.05) compared with control. In a second study, birds treated with NP122 (identified as Bacillus subtilis) had significantly lower (P < 0.05) cecal ST than control and benefitted BW gain irrespective of the presence or absence of a Salmonella challenge. In conclusion, NP122 markedly reduced ST recovery and increased BW gain in both chicks and poults. This provides preliminary evidence that this isolate may have potential use as a DFM in poultry.