Adding organic acids to piglet diets is known to be helpful in overcoming postweaning syndrome, and butyric acid is known to be the main energy source for the epithelial cells of the large intestine and the terminal ileum. This study investigated the effect of sodium butyrate (SB) on in vitro and in vivo swine microflora, piglet growth performance, and intestinal wall morphology. During a 24-h in vitro cecal fermentation, total gas production and maximal rate of gas production were reduced linearly by SB (P < 0.001). Ammonia in cecal liquor was increased linearly by SB after 4, 8, and 24 h of fermentation (P < 0.001). In the in vivo study, 48 piglets housed in individual crates were allotted to 4 treatment groups (12 animals per treatment) for 6 wk. Piglets received a basal diet with a) no addition (control), or with SB at b) 1,000 ppm, c) 2,000 ppm, or d) 4,000 ppm. After 6 wk, 6 animals per treatment were killed, and samples of intestinal content and mucosa were collected. Sodium butyrate did not improve the animal growth performance. In the cecum, SB increased pH and isobutyric acid concentration (linear, P < 0.05) and tended to increase ammonia concentration (P = 0.056). Intestinal counts of clostridia, enterobacteriaceae, and lactic acid bacteria as well as intestinal mucosal morphology were not affected by feeding SB. This study showed that SB influenced the cecal microflora in an in vitro system, reducing the total gas production but increasing ammonia concentrations. When fed to piglets, SB did not improve the animal growth performance, increased cecal pH, and tended to increase cecal ammonia concentrations. Further studies will be needed to better understand the mechanisms underlying the effects observed when SB is fed to piglets.