The effects of four metal ions (Ca2+, Ni2+, Mn2+ and Cu2+) were evaluated on growth and production of antifungal compounds by Paenibacillus polymyxa SQR-21 and a quadratic predictive model was developed using response surface methodology (RSM). The results revealed, Mn2+ and Ni2+ showed most positive synergistic interactive affect on production of antifungal compounds followed by the positive interactive synergistic affect of Cu2+ and Ni2+ and then Mn2+ and Cu2+. While the interactive effect of Ca2+ with all other three metals inhibited the production of antifungal compounds. The Mn2+ (P = 0.0384), Ni2+ (P = 0.0004) and Cu2+ (P = 0.0117) significantly affected the production of antifungal compounds while the effect of Ca2+ (P = 0.1851) was less significant. The maximum growth (OD600 = 1.55) was obtained at 500 (0), 125 (0). 100 (-2) and 37.5 (0) mu M levels and the maximum size of inhibition zone (31 mm) was measured at 400 (-1), 150 (1). 400 (1) and 25 mu M (-1) levels of Ca2+, Mn2+, Ni2+ and Cu2+, respectively. The RSM model provided an easy and effective way to determine the interactive effect of metal ions on production of antifungal compounds by P. polymyxa SQR-21 so that optimum media recipes can be developed to produce maximum amounts of antifungal compounds under laboratory and commercial fermentation conditions. (C) 2009 Elsevier Ltd. All rights reserved.