Individuals increasingly have encountered messages that mental illness is explained by biological factors such as chemical imbalance or genetic abnormality. Many assumed this “biological turn” would lessen stigma toward mental illness, but stigma generally has remained stable or even increased. Given how nonbiological illness explanations (e.g., way one is raised, bad character, life stressors) often are endorsed even among those who support biological explanations, we contend that combinations or configurations of beliefs integrating distinct types of explanation may hold a key to understanding why biological beliefs have not succeeded in lessening stigma. Using qualitative comparative analysis (QCA) on national vignette data (2006 General Social Survey; N = 968), we find that not blaming an individual’s character is essential to lowering depression stigma whenever biological explanations also are endorsed and that blaming character unconditionally contributes to stigmatizing alcoholism. For schizophrenia and alcoholism, biological explanations may lower stigma contingent on several other beliefs.