With the increasing application of genomic and proteomic technologies to the research of neurological and psychiatric disorders it has become imperative that the postmortem tissue utilized be of the highest quality possible. Every step of the research design, from identifying donors, acquiring sufficient information for accurate diagnosis, to assessing tissue quality has to be carefully considered. In order to obtain high-quality RNA and protein from the postmortem brain tissue a standardized system of brain collection, dissection, and storage must be employed and key ante- and postmortem factors must be considered. Reliable RNA expression and protein data can be obtained from postmortem brains with relatively long postmortem intervals (PMIs) if the agonal factors and acidosis are not severe. While pH values are correlated with RNA integrity number (RIN), a higher pH does not guarantee intact RNA. Consequently RNA integrity must be assessed for every case before it is included in a study. An analysis of anti- and postmortem factors in a large brain collection has revealed that several diagnostic groups have significantly lower pH values than other groups, however, they do not have significantly lower RIN values. Moreover, the lower pH of these groups is not entirely due to agonal factors and/or smoking, indicating that these subjects may have additional metabolic abnormalities that contribute to the lower pH values.