['One of the main distinctions between different theories describing protein folding is the predicted sequence of secondary structure formation and compaction during the folding process. Whether secondary structure formation precedes compaction of the protein molecules or secondary structure formation is driven by a hydrophobic collapse cannot be decided unequivocally on the basis of existing experimental data.', 'In this study, we investigate the refolding of chemically denatured, disulfide-intact ribonuclease A (RNase A) by monitoring compaction and secondary structure formation using stopped-flow dynamic light scattering and stopped-flow CD, respectively. Our data reveal the formation of a considerable amount of secondary structure early in the refolding of the slow folding species of RNase A without a significant compaction of the molecules. A simultaneous formation of secondary structure and compaction is observed in the subsequent rate-limiting step of folding.'] Is initial hydrophobic collapse necessary for folding RNase A?