To test whether a widely used model of adjustment to illness, the self-regulatory model, explains the patterns of distress during acute hematopoietic stem cell transplantation (HSCT). According to the model, perceptions of HSCT, coping, and coping appraisals are associated with distress. .Longitudinal, correlational. .The Centre for Clinical Haematology at Nottingham City Hospital and the Department of Haematology at Royal Hallamshire Hospital in Sheffield, both in the United Kingdom. .45 patients receiving mostly autologous transplantations for a hematologic malignancy. .Patients were assessed at baseline, on transplantation day, and two and four weeks after transplantation using three questionnaires.Psychological distress, including depression, anxiety, stress, and overall distress (DASS-21); use of different coping styles (Brief COPE); and perceptions of HSCT and coping appraisals (Brief IPQ). .As suggested by the self-regulatory model, greater distress was associated with negative perceptions of HSCT, controlling for the effects of confounding variables. Mixed support was found for the model's predictions about the impact of coping styles on distress. Use of active and avoidant coping styles was associated with more distress during the acute phase after HSCT. .Negative perceptions of HSCT and coping contribute to psychological distress during the acute phase after HSCT and suggest the basis for intervention. .Eliciting and discussing patients' negative perceptions of HSCT beforehand and supporting helpful coping may be important ways to reduce distress during HSCT.