This paper describes the use of a novel porous matrix, Porocell, for high density, tissue-like culture of two insulinoma cell lines, CRI-D2 and CRI-D11. Both these cell lines have previously been shown not to secrete insulin in response to glucose. Porocell is a macro-porous, polymeric material manufactured in the shape of discs that are 6.2 mm in diameter and 2 mm in thickness. Insulinoma cells were cultured in two different mini-bioreactors, each containing six Porocell discs inoculated with 2.5 x 10(6) cells per disc. In surface aerated, stirred bioreactors, the insulinoma cells grew as closely packed dense cell sheets penetrating deep into the pores of Porocell. In a second type of system, a packed-bed perfused mini-bioreactor, flat, extended monolayers of cells were observed growing throughout the Porocell matrix. In both bioreactor configurations, viable cell populations were maintained for 30 days because of the excellent oxygen and nutrient transfer properties of Porocell. CRI-D2 insulinoma cells cultured in static flasks and on Porocell did not show any insulin secretion in response to 30 min exposures in media supplemented with 5.5-16.7 mmol dm(-3) glucose. However, in long term (14-19 day) cultures, CRI-D2 cells growing in Porocell secreted low, but measurable amounts (25-35 pmol dm(-3)) of insulin in medium supplemented with elevated (14.5 mmol dm(-3)) glucose concentrations. The glucose uptake rates of cells cultured in 4.0 mmol dm(-3) glucose increased linearly from 1.0 to 2.3 mmoldm(-3) day(-1) over a period of 19 days. At 14.5 mmol dm(-3) glucose concentration, the uptake rate increased from 1.0 to 7.05 mmol dm(-3) day(-1) over the same period of culture. Contrary to previous studies, we have demonstrated that the CRI-D2 cell line cultured at high cell density in Porocell is capable of secreting insulin when exposed to prolonged and elevated concentrations of glucose. The Porocell mini-bioreactors are easy to use, robust systems that can be used for long-term studies of primary and tumorgenic islet cell function and response to secretagogues.