The goal of the present study was to assess the effect of macropore size on the in vivo behavior of ceramic scaffolds. For that purpose, beta-tricalcium phosphate (beta-TCP) cylinders with four different macropore sizes (150, 260, 510, and 1220 microm) were implanted into drill hole defects in cancellous bone of sheep and their resorption behavior was followed for 6, 12 and 24 weeks. The scaffolds were evaluated for biocompatibility, and new bone formation was observed macroscopically, histologically and histomorphometrically. Histomorphometrical measurements were performed for the whole defect area and for the area subdivided into three concentric rings (outer, medial, and inner ring). All implants were tolerated very well as evidenced by the low amount of inflammatory cells and the absence of macroscopic signs of inflammation. Resorption proceeded fast since less than 5% ceramic remained at 24-week implantation. Hardly any effect of macropore size was observed on the in vivo response. Samples with an intermediate macropore size (510 microm) were resorbed significantly faster than samples with smaller macropore sizes (150 and 260 microm). However, this fast resorption was associated with a lower bone content and a higher soft tissue content. At 12 and 24 weeks, the latter differences had disappeared. Bone was more abundant in the outer ring than in the rest of the blocks at 6 weeks, and in the outer and medial ring compared to the inner ring at 12 weeks.