IMPORTANCE In 1939, English mathematician, geneticist, and psychiatrist Lionel Sharples Penrose hypothesized that the numbers of psychiatric hospital beds and the sizes of prison populations were inversely related; 75 years later, the question arises as to whether the hypothesis applies to recent developments in South America. OBJECTIVE To explore the possible association of changes in the numbers of psychiatric hospital beds with changes in the sizes of prison populations in South America since 1990. DESIGN, SETTING, AND PARTICIPANTS We searched primary sources for the numbers of psychiatric hospital beds in South American countries since 1990 (the year that the Latin American countries signed the Caracas Declaration) and compared these changes against the sizes of prison populations. The associations between the numbers of psychiatric beds and the sizes of prison populations were tested using fixed-effects regression of panel data. Economic variables were considered as covariates. Sufficiently reliable and complete data were obtained from 6 countries: Argentina, Bolivia, Brazil, Chile, Paraguay, and Uruguay. MAIN OUTCOMES AND MEASURES The numbers of psychiatric beds and the sizes of prison populations. RESULTS Since 1990, the numbers of psychiatric beds decreased in all 6 countries (ranging from −2.0% to −71.9%), while the sizes of prison populations increased substantially (ranging from 16.1% to 273.0%). Panel data regression analysis across the 6 countries showed a significant inverse relationship between numbers of psychiatric beds and sizes of prison populations. On average, the removal of 1 bed was associated with 5.18 more prisoners (95% CI, 3.10-7.26; P = .001), which was reduced to 2.78 prisoners (95% CI, 2.59-2.97; P < .001) when economic growth was considered as a covariate. The association between the numbers of psychiatric beds and the sizes of prison populations remained practically unchanged when income inequality was considered as a covariate (−4.28 [95% CI, −5.21 to −3.36]; P < .001). CONCLUSIONS AND RELEVANCE Since 1990, the numbers of psychiatric beds have substantially decreased in South America, while the sizes of the prison populations have increased against a background of strong economic growth. The changes appear to be associated because the numbers of beds decreased more extensively when and where the sizes of prison populations increased. These findings are consistent with and specify the assumption of an association between the numbers of psychiatric beds and the sizes of prison populations. More research is needed to understand the drivers of the capacities of psychiatric hospitals and prisons and to explore reasons for their association.