The quality of QSAR (Quantitative Structure-Activity Relationships) predictions depends on a large number of factors including the descriptor set, the statistical method, and the data sets used. Here we study the quality of QSAR predictions mainly as a function of the data set and descriptor type using partial least squares as the statistical modeling method. The study makes use of the fact that we have access to a large number of data sets and to a variety of different QSAR descriptors. The main conclusions are that the quality of the predictions depends both on the data set and the descriptor used. The quality of the predictions correlates positively with the size of the data set and the range of biological activities. There is no clear dependence of the quality of the predictions on the complexity of the data set. All of the descriptors tested produced useful predictions for some of the data sets. None of the descriptors is best for all data sets; it is therefore necessary to test in each individual case, which descriptor produces the best model. In our tests, 2D fragment based descriptors usually performed better than simpler descriptors based on augmented atom types. Possible reasons for these observations are discussed.