Optimising microencapsulation technology towards the effective clinical transplantation has created the need for highly biocompatible alginates. Therefore, in this study the biocompatibility of different beads prepared from alginates with varying average molecular weight was examined. In some experiments the beads were covered with a multilayer membrane surrounded by an alginate layer. First of all, we found that beads made of a lower weight average alginate elicted a much stronger fibrotic response compared to beads made of a higher weight average alginate (LV-alginate > MV-alginate). The results were confirmed by the observation that the extent of tissue fibrosis was significantly increased in multilayer capsules made of an alginate with a lower weight average (core and surface LV-alginate, Mw 0.7-1 * 10(6) g/mol, viscosity of a 0.1% solution 1-2.5 mPa s(-1)) compared to multilayer capsules made of an alginate with a higher weight average (core and surface MV-alginate; Mw 1.2-1.3 * 10(6) g/mol, viscosity of a 0.1% solution 5-7 mPa s(-1)). It should be stressed, that the pro-fibrotic effect of the LV-alginate alginate in the core was only partially reversed by a MV-alginate on the surface of the multilayer capsules. On the basis of the raised data, it can be assumed that the molecular weight average of the alginates have an decisive effect on the biocompatibility. Therefore, it seems to be recommendable to reduce the low molecular weight fractions of the alginate during the purification process to improve the biocompatibility.