Employees at the KwaZulu-Natal Department of Health have called on premier Sbu Ndebele to stop departmental head Busi Nyembezi from "destroying" the department.
Several senior managers have since resigned from the department, citing differences with Nyembezi as the reason.
In a letter to Ndebele, senior staff members alleged that Nyembezi was on "a mission to destroy the department".
The letter said key resignations within the department in recent months were worrying.
Between November and last month two senior managers resigned. Sibongile Zungu, general manager in health service resigned first and was followed by Mbali Thusi, deputy director for communications.
Departmental spokesman Mandla Mathaba is said to be on unpaid leave after an alleged fallout with Nyembezi.
Ndebele's office said it would respond after receiving the letter.