In this study, mathematical modeling of a horizontal tubular loop bioreactor (HTLB) was considered for biomass production from natural gas. Gas inlet segments, static mixers, gas-liquid separator, and liquid pump of the HTLB were mathematically modeled according to the ideal stirred reactors, and the horizontal parts, riser, and down-corner sections were modeled in line with the dispersed plug-flow reactors as well. The set of ordinary and partial differential equations were coupled to calculate the oxygen and methane concentrations in the liquid through the length of bioreactor and time. Moreover, the tuned kinetic and hydrodynamic parameters of SCP process in the HTLB were determined based on the mathematical model at various operational conditions. The model was validated by considering experimental dissolved oxygen, methane, and biomass concentrations in liquid at different ratios of air to methane and liquid flow rates. The results showed satisfactory agreement between the developed model and the experimental data. (C) 2010 Elsevier Ltd. All rights reserved.