The focus of the current study was to perform an experimental investigation and computational fluid dynamic (CFD) simulation of flow hydrodynamics in a forced-liquid horizontal tubular loop bioreactor for the production of biomass. The simulations were performed using the FLUENT commercial CFD package, a segregated unsteady solver and a two-phase Eulerian multiphase model. To validate the simulation results, several experiments were performed in a pilot bioreactor. In addition, the design of experiments methodology using a Taguchi orthogonal array (OA) was applied to evaluate the influence of four factors on the hydrodynamic behavior of the bioreactor. The effective parameters considered for optimization were air inlet velocity, liquid inlet velocity, bubble diameter, and viscosity. An L-9 OA was used to conduct the Taguchi experiments to study the significance of these parameters and the possible effects of any two-factor interactions. The optimum conditions and most significant process parameters affecting the hydrodynamic behavior were determined using an analysis of variance model. The results showed that the liquid inlet velocity had the most influence on the air volume fraction in the bioreactor. A subsequent confirmatory test demonstrated that the results were within the confidence interval. (C) 2010 Elsevier B.V. All rights reserved.